A promising approach to treating and preventing genetic diseases and disorders is delivery of therapeutic agents with a gene therapy vector such as a viral vector. Illustrative examples of viral vectors suitable for gene therapy include but are not limited to retroviral vectors, lentiviral vectors, adenovirus vectors, herpes virus vectors, alphaviruses vectors, and adeno-associated virus (AAV) vectors. AAV is a 4.7 kb, single stranded DNA virus. Recombinant vectors based on AAV are associated with excellent clinical safety, since wild-type AAV is nonpathogenic and has no etiologic association with any known diseases. In addition, AAV offers the capability for highly efficient gene delivery and sustained transgene expression in numerous tissues, including eye, muscle, lung, and brain. Furthermore, AAV has shown promise in human clinical trials. One example is Leber's congenital amaurosis in which patients treated with a therapeutic delivered by a single subretinal administration of an rAAV vector have experienced sustained clinical benefit from expression of the therapeutic agent for more than four years from the initial date of treatment.
Certain challenges that remain with regard to the design of viral vectors for use in gene therapy include optimizing viral cell tropism and reducing anti-viral or neutralizing host antibody responses. For certain viral vectors, such as AAV, cell tropism and neutralizing antibody responses result largely from the structure of the viral capsid protein. Thus, there is a need in the art for improved tools to screen for mutant viral capsids with desired properties. The present invention addresses these and other issues.